| 主权项 |
1. A compound of formulae I(A-E) having the following structure: wherein: the carbon atom designated * is in the R or S configuration; and X represents a 5- or 6-membered aromatic monocyclic carbocycle or heterocycle selected from the group consisting of phenyl, pyridyl, 2-oxo-pyridin-1(2H)-yl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, triazolyl, and tetrazolyl, substituted from 1 to 4 times with substituents as defined below in R14, or other 5- or 6-membered aromatic monocyclic carbocycles or heterocycles containing 1-4 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, substituted from 1 to 4 times with substituents as defined below in R14; or X is a [5,5]-, [6,5]-, [6,6]-, or [6,7]-fused bicyclic carbocycle or heterocycle selected from the group consisting of indenyl, benzofuranyl, benzothiophenyl, indolyl, isoindolyl, benzooxazolyl, benzothiazolyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, benzoimidazolyl, benzotriazolyl, naphthyl, quinolinyl, isoquinolinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 4H-chromenyl, indolizinyl, quinolizinyl, 6aH -thieno[2,3-d]imidazolyl, 1H-pyrrolo[2,3-b]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]furanyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, furo[2,3-b]pyridinyl, furo[3,2-b]pyridinyl, thieno[3,2-d]pyrimidinyl, furo[3,2-d]pyrimidinyl, thieno[2,3-b]pyrazinyl, benzo[c][1,2,5]oxadiazolyl, benzo[c][1,2,5]thiadiazolyl, imidazo[1,2-a]pyrazinyl, 3,3-dimethyl-2-oxoindolinyl, benzo[c][1,2,5]oxadiazolyl, benzo[c][1,2,5]thiadiazolyl, [1,2,4]triazolo[4,3-a]pyrazinyl, and 3-oxo-[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl, substituted from 1 to 4 times with substituents as defined below in R14, or other [5,5]-, [6,5]-, [6,6]-, or [6,7]-fused bicyclic carbocycles or heterocycles containing 1-5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, substituted from 1 to 4 times with substituents as defined below in R14; R1 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, where each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, where each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; or R2 is gem-dimethyl; R3, R5, and R6 are each independently selected from the group consisting of H, halogen, —OR12, —S(O)nR13, —CN, —C(O)R13, —NR10R11, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; or R3, R5, and R6 are each independently a 5- or 6-membered monocyclic carbocycle or heterocycle, optionally substituted from 1 to 4 times with substituents as defined below in R14; R4 is H, halogen, —OR12, —S(O)nR13, —CN, —C(O)R13, —NR C10R11, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, where each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; R4 is a bridged bicyclic ring containing 6-12 carbon atoms and optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, where the bridged bicyclic ring is optionally substituted from 1 to 3 times with substitutents selected from the group consisting of C1-C3 alkyl, —C(O)R13, and —S(O)nR13; or R4 is an aromatic monocyclic or bicyclic carbocycle or an aromatic or non-aromatic monocyclic or bicyclic heterocycle selected from the group consisting of phenyl, pyridyl, 2-oxo-pyridin-1(2H)-yl, pyrimidinyl, pyridazinyl, 6-oxopyridazin-1(6H)-yl, pyrazinyl, triazinyl, furanyl, pyrrolyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, indenyl, indolyl, isoindolyl, benzofuranyl, benzothiophenyl, indolinyl, indazolyl, benzimidazolyl, benzooxazolyl, benzothiazolyl, benzoisoxazolyl, benzoisothiazolyl, benzotriazolyl, naphthyl, quinolinyl, isoquinolinyl, quinazolinyl, cinnolinyl, pthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 4H-chromenyl, indolizinyl, quinolizinyl, 6aH-thieno[2,3-d]imidazolyl, 1H-pyrrolo[2,3-b]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, thieno[2,3 -b] furanyl, thieno[2,3 -b] pyridinyl, thieno[3,2-b]pyridinyl, furo[2,3-b]pyridinyl, furo[3,2-b] pyridinyl, thieno[3,2-d]pyrimidinyl, furo[3,2-d]pyrimidinyl, thieno[2,3-b]pyrazinyl, imidazo[1,2-a]pyrazinyl, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazinyl, 3,3-dimethyl-2-oxoindolinyl, benzo[c][1,2,5]oxadiazolyl, benzo[c][1,2,5]thiadiazolyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, [1,2,4]triazolo[4,3-a]pyrazinyl, 3-oxo41,2,4]triazolo[4,3-a]pyridin-2(3H)-yl, and 2-oxooxazolidin-3-yl, or other 5- or 6-membered aromatic monocyclic carbocycles or aromatic or non-aromatic monocyclic or bicyclic heterocycles, or [5,5]-, [6,5]-, [6,6]-, or [6,7]-fused bicyclic carbocycles or heterocycles containing 1-5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, substituted from 1 to 4 times with substituents as defined below in R14; provided that for compounds of formula IA, X is substituted phenyl and R4 is substituted aromatic monocyclic or bicyclic carbocycle or heterocycle; provided that for compounds of formula IB, X is substituted aromatic bicyclic carbocycle or heterocycle and R4 is substituted aromatic monocyclic or bicyclic carbocycle or heterocycle; provided that for compounds of formula IC, X is substituted phenyl and R4 is H, —OR R12, —S(O)nR13, C(O)R13, —NR10R11, —CN, halogen, or C1-C6 alkyl, where C1-C6 alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; provided that for compounds of formula ID, X is substituted aromatic bicyclic carbocycle or heterocycle and R4 is H, —OR12, —S(O)nR13, C(O)R13, —NR10R11, —CN, halogen, or C1-C6 alkyl, where C1-C6 alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; and provided that for compounds of formula IE, X is substituted aromatic monocyclic heterocycle and R4 is substituted aromatic monocyclic or bicyclic carbocycle or heterocycle; R7 is selected from the group consisting of H, —S(O)nR13, —C(O)R13, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where each of C1 -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; R8 is selected from the group consisting of H, halogen, —OR12, —S(O)nR13, —CN, —C(O)R13, —NR10R11, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; or R7 and R8 are gem-dimethyl, with the proviso that only one of R7 and R8 is gem-dimethyl; R9 is H, halogen , —OR12, —SR10, C1-C6alkyl, —CN, or NR10R11, where C1-C6 alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; R10 and R11 are each independently selected from the group consisting of H, —C(O)R13, C1-C6 alkyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where each of C1-C6 alkyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; R10 and R11 are each independently selected from the group consisting of phenyl, benzyl, and other 5- or 6-membered monocyclic heterocycles, where each of the phenyl, benzyl, and 5- or 6-membered monocyclic heterocycle is optionally substituted from 1 to 3 times with substituents as defined below in R14; R10 and R11 are taken together with the nitrogen to which they are attached to form a saturated or partially saturated monocyclic or fused bicyclic heterocycle selected from the group consisting of piperidine, pyrrolidine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 3-oxomorpholino, 3-oxothiomorpholino, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, and other monocyclic or fused bicyclic heterocycles containing 1-4 heteroatoms selected from oxygen, nitrogen and sulfur, and is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OR12, —NR12R13, —S(O)nR13, —C(O)R13, and C1-C4 alkyl, where each of C1-C4 alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; R10 and R11 are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperazine, 2-oxopiperazinyl, 2-oxo-1,4-diazepanyl, 5-oxo-1,4-diazepanyl, 1,4-diazepane, and other heterocycles containing one additional nitrogen atom in the ring, where the heterocycle is optionally substituted on a ring carbon with from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OR12, —NR12R13, —S(O)nR13, —C(O)R13, and C1-C4 alkyl, or on the additional nitrogen atom from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of S(O)nR13, —C(O)R13, and C1-C4 alkyl, wherein each of C1-C4 alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; R10 and R11 are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperazine, 2-oxopiperazinyl, 2-oxo-1,4-diazepanyl, 5-oxo-1,4-diazepanyl, 1,4-diazepane, and other heterocycles containing one additional nitrogen atom in the ring, where the heterocycle is optionally substituted on the additional nitrogen atom with a substituent selected independently at each occurrence thereof from the group consisting of phenyl, benzyl, and 5- or 6-membered aromatic heterocycles containing 1-3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, where each of the phenyl, benzyl, and 5- and 6-membered heterocycle is optionally substituted from 1 to 3 times with substituents as defined below in R14; or when R4 is —NR10R11 or —C(O)NR10R11, either R or R11 is a bridged bicyclic ring containing 6-12 carbon atoms and optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, where the bridged bicyclic ring is optionally substituted from 1 to 3 times with substituents selected from the group consisting of C1-C3 alkyl, —C(O)R13, and —S(O)nR13, or either R10 or R11 is a C1-C3 alkyl substituted with a bridged bicyclic ring containing 6-12 carbon atoms and optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, where the bridged bicyclic ring is optionally substituted from 1 to 3 times with substitutents selected from the group consisting of C1-C3 alkyl, —C(O)R13, and —S(O)nR13; R12 is selected from the group consisting of H, C1-C4 alkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and —C(O)R13, where each of C1-C4 alkyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; R13 is selected from the group consisting of H, —NR10R11, C4 alkyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where each of C1-C4 alkyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; or R12 and R13 are each independently selected from the group consisting of phenyl, benzyl, pyridazinyl, pyrimidinyl, pyrazinyl, 5- or 6-membered aromatic monocyclic heterocycles, and [5,5]-, [6,5]-, [6,6]-, or [6,7]-fused bicyclic carbocycles or heterocycles containing 1-5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, optionally substituted from 1 to 4 times with substituents as defined below in R14; or R12 and R13 are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperidine, pyrrolidine, piperazine, 1,4-diazepane, morpholine, thiomorpholine, and other heterocycles containing 1-4 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, where the heterocycle is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OR10, —S(O)nR10, —C(O)R10, —C(O)NR10R11 and C1-C4 alkyl, where each of C1-C4 alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; n is 0, 1, or 2; R14 is independently selected at each occurrence from a substituent in the group consisting of halogen, —NO2, —OR12, —NR10R11, —NR12C(O)2R13, —NR12C(O)NR12R13, —S(O)nR13, —CN, —C(O)R13, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R15; and R15 is independently selected at each occurrence from a substituent in the group consisting of —CN, halogen, C(O)R13, C1-C3 alkyl, —OR12, —NR10R11, —S (O)nR13, aryl, and heteroaryl, where each of the aryl or heteroaryl groups is optionally substituted from 1 to 4 times with substituents as defined above in R14; or an oxide thereof, or a pharmaceutically acceptable salt thereof. |
